The place of TKI in the treatment of EGFR mutation-positive lung cancer

Fumihiro Oshita, Shuji Murakami

Abstract

About half of all Asian patients with non-small cell lung cancer (NSCLC) have tumors that are positive for epidermal growth factor receptor (EGFR) mutation, for which tyrosine kinase inhibitors (TKI) such as gefitinib or erlotinib are effective. Gefitinib has been shown to be a useful second-line treatment for NSCLC after platinum-based chemotherapy [1], and some small-scale studies have also examined its activity as a first-line treatment for NSCLC, demonstrating a response rate of about 20% [2, 3], which is similar to that of other anticancer drugs for NSCLC. However, gefitinib has failed to exert any additional effect when combined with platinum-based chemotherapy as a first-line treatment for NSCLC [4, 5]. On the other hand, two biological studies have demonstrated that gefitinib is effective in specifically targeting the EGFR gene with deletion in exon 19 or point mutation in exon 21, and tumor regression induced by gefitinib in NSCLC patients has been shown to be correlated with the presence of these mutations in lung tumors [6, 7]. A Japanese study has demonstrated that patients with postoperative recurrence of EGFR mutation-positive NSCLC showed a good tumor response to gefitinib and achieved longer survival than patients whose tumors lacked EGFR mutation [8]. A study designed to compare carboplatin plus paclitaxel with gefitinib for chemo-naïve Asian patients with both EGFR mutation-positive and -negative NSCLC demonstrated that patients with EGFR mutation-positive tumors achieved significantly longer overall and progression-free survival with gefitinib than with carboplatin plus paclitaxel in subset analysis [9]. Thereafter, two large studies designed to compare platinum-based chemotherapy with gefitinib therapy for chemo-naïve NSCLC patients with EGFR mutation were performed in Japan. In both studies, the progression-free survival achieved with gefitinib was about twice as long as that achieved with standard platinum-based chemotherapy [10, 11]. These data indicated that gefitinib is an effective first-line chemotherapy for NSCLC harboring EGFR mutation.

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